Lysosomal changes in skeletal muscles during the repair of exercise injuries in muscle fibers.

Lysosomal changes were recorded in the skeletal muscles of mice and rats during the repair of muscle fiber injuries caused by a single bout of prolonged running. One purpose of the study was to characterize cellular and compartmental distributions of lysosomal enzymes and to investigate ultrastructural changes in the lysosomal system associated with the appearance and repair of muscle fiber injuries. Furthermore, the level of muscle fiber injuries was correlated with the lysosomal enzyme response and the indices obtained were utilized in the evaluation of the pathogenesis of exercise myopathy. The main results were: Heavy physical exertion caused scattered necrotic injuries of muscle fibers and inflammation in several skeletal muscles. The most susceptible muscles to exercise injuries were the red deep parts of quadriceps femoris muscle and the soleus and tibialis anterior muscles. The total activities of several lysosomal acid hydrolases, in particular those of beta/-glucuronidase, cathepsin C and arylsulphatase, strongly increased during the repair of exercise injuries. The highest responses occurred 3-5 days after exertion and the degree of enzyme responses correlated significantly with the level of histological injuries. The histochemical staining intensities of beta-N-acetylglucosaminidase and beta-glucuronidase were highest 3 and 5 days after exertion. An increased staining intensity occurred in the inflammatory phagocytes and in the surviving muscle fibers, especially in the red muscle fibers close to necrotic foci. An autophagic response occurred in the muscle fibers close to necrotic foci 2-7 days after exertion. Autophagic vacuoles were frequently small and contained different cellular structures at various stages of degradation. The number of lysosome-like bodies, Golgi complexes and multilamellar bodies also increased. Macrophages removed the debris of necrotic muscle fibers by heterophagic uptake 2-5 days after exertion. The unsedimentable and releasable activities of acid hydrolases increased more prominently than those of the total activities in homogenates and reached their highest values 3 days after exertion. The proportional distribution of various acid hydrolases to unsedimentable, releasable and bound fractions varied strikingly but remained appreciably stable throughout the exercise myopathy. The content of lysosomal phosphomannosyl-enzyme receptors in the membrane fraction was unchanged 0-3 days after exertion but a small increase occurred later. The endogenous receptor-bound activity of beta-N-acetylglucosaminidase was considerably increased 1-5 days after exertion but decreased later to the control level.(ABSTRACT TRUNCATED AT 400 WORDS)